Abstract

Neonatal intermittent hypoxia (IH) or apnea afflicts 70% to 90% of all preterm infants <28 weeks gestation, and is associated with severe retinopathy of prematurity (ROP). We tested the hypotheses that coenzyme Q10 (CoQ10) or omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplementation during neonatal IH reduces the severity of oxygen-induced retinopathy (OIR). Newborn rats were exposed to two IH paradigms: (1) 50% O2 with brief hypoxia (12% O2); or (2) 21% O2 with brief hypoxia, until postnatal day 14 (P14), during which they received daily oral CoQ10 in olive oil, n-3 PUFAs in fish oil, or olive oil only and compared to room air (RA) treated groups. Pups were examined at P14, or placed in RA until P21. Retinal angiogenesis, histopathology, and morphometry were determined. Both IH paradigms produced severe OIR, but these were worsened with 50/12% O2 IH. CoQ10 and n-3 PUFAs reduced the severity of OIR, as well as ocular growth factors in both IH paradigms, but CoQ10 was more effective in 50/12% O2 IH. Supplementation with either CoQ10 or n-3 PUFAs targeting IH-induced retinal injury is individually effective for ameliorating specific characteristics consistent with ROP. Given the complexity of ROP, further studies are needed to determine whether combined CoQ10 and n-3 PUFAs supplementation would optimize their efficacy and result in a better outcome.

Highlights

  • Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide [1].Late complications of ROP include the development of other ocular diseases such as glaucoma, amblyopia, strabismus, myopia, and retinal detachment [2,3], resulting in financial and emotional burdens [4,5,6,7]

  • Neonatal intermittent hypoxia (IH) is defined as brief, recurrent arterial oxygen desaturations [12,13,14,15,16], and is one of the major factors associated with severe ROP in extremely low gestational age neonates (ELGANs) requiring oxygen therapy [17,18,19,20,21,22,23]

  • The first evidence of the beneficial effects of coenzyme Q10 (CoQ10) or n-3 polyunsatuarated fatty acids (PUFAs) supplementation during neonatal IH is demonstrated in Table 1. n-3 PUFAs accelerated visual maturation and shortened the caecal period in over 80% of treated rats in room air (RA) and 50/12% O2 IH, and to a lesser degree in

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Summary

Introduction

Retinopathy of prematurity (ROP) is a leading cause of childhood blindness worldwide [1].Late complications of ROP include the development of other ocular diseases such as glaucoma, amblyopia, strabismus, myopia, and retinal detachment [2,3], resulting in financial and emotional burdens [4,5,6,7]. ROP is a developmental vascular disorder characterized by the abnormal growth of retinal blood vessels in extremely low gestational age neonates (ELGANs) who are ≤28 weeks gestation [8,9,10,11]. Antioxidants 2018, 7, 160 oxidative distress, inflammation, poor nutrition, dysregulated growth factors, and neonatal intermittent hypoxia (IH), contribute to its severity. Neonatal IH is defined as brief, recurrent arterial oxygen desaturations [12,13,14,15,16], and is one of the major factors associated with severe ROP in ELGANs requiring oxygen therapy [17,18,19,20,21,22,23].

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